Abstract A107: Updated results from a study of evalstotug (BA3071), an anti–CTLA-4 conditionally active biologic, in melanoma

Abstract Background: Commercially available CTLA-4 antibodies are associated with a high incidence of immune mediated adverse events. Evalstotug (BA3071) is a conditionally active biologic (CAB) anti–CTLA-4 monoclonal antibody that blocks the interaction of CTLA-4 with its ligands in the low-pH conditions of the tumor microenvironment. CABs are not masked or caged and do not require enzymatic cleavage for activation. They are reversibly bound in the acidic tumor microenvironment, which is expected to reduce off-tumor immune-related adverse events, enhance host immunity, avoid tissue-mediated drug disposition, and improve pharmacokinetics. This study evaluated the safety and antitumor activity of evalstotug ± anti-PD-1 therapy in patients (pts) with advanced solid tumors. Methods: In an ongoing cohort for adult 1st line pts, treatment naïve unresectable/metastatic melanoma with measurable disease per RECIST v1.1 received evalstotug (350 – 1000 mg) every 3 weeks (Q3W) + pembrolizumab 200 mg Q3W. Safety was assessed using the NCI CTCAE v5, and efficacy was assessed using RECIST v1.1, with response assessment performed Q6W for 24 weeks, then Q12W. Results: An initial eight pts were treated with evalstotug (350-1000 mg) + anti-PD-1. Seven patients received prior neoadjuvant/adjuvant immunotherapy. Pts received a median of 9 doses. Most related treatment-emergent adverse events (TEAEs) were low grade. Two pts experienced grade 3 related TEAEs (1. colitis and 2. pneumonitis and pancreatitis) that led to discontinuation of treatment, but which quickly resolved. No grade 4/5 related TEAEs were observed to date. All patients experienced tumor volume reduction and those who were dose escalated were able to regain tumor control. Four of 8 pts responded - 3 PRs, 1 CR and 4 pts experienced stable disease. Conclusions: All (8/8) metastatic and unresectable melanoma pts safely achieved tumor reduction with evalstotug + anti-PD-1, including patients with only 1 scan, which will be further updated. It was notable that intrapatient evalstotug dose escalation safely re-attained tumor control, suggesting increasing evalstotug exposure can drive improved antitumor activity, even after months on anti-CTLA4 therapy. No new safety signals were identified, and the incidence and severity of imAEs was in line with previous reports, consistent with evalstotug’s tumor selectivity. Dose optimization is actively underway, and pivotal trial initiation is anticipated in 2025. Citation Format: Inderjit Mehmi, Jennifer E Selfridge, Ankit Mangla, Matthew H Taylor, Constantine Albany, Vineet Kwatra, Jacob Thomas, Siwen Hu-Lieskovan, Kyechin Chen, Judith Llorin-Sangalang, Kartik Aysola, Omid Hamid. Updated results from a study of evalstotug (BA3071), an anti–CTLA-4 conditionally active biologic, in melanoma [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A107.